Solid tumor malignancies accounts for 85% cancer mortality that in 2004 was responsible for 23% of all deaths in US. Current approaches for the treatment of solid tumor malignancies with established agents and with the new targeted agents used alone and in combination are limited, in part, by inability to deliver cytotoxic agents selectively to the tumor tissue in sufficient concentrations critical for tumor cell kill that translate into meaningful and durable responses. Evidence of this limitation is derived from the following: 1) response of solid tumor malignancies to existing therapy are relatively poor and don't provide long and sustained cures; 2) drug concentration used in vitro (in culture in test tube) to produce significant growth inhibition that correlates with inhibition of specific target and/or pathways is difficult to achieve in tumor cells in vivo (whole organism—animal or human) at their recommended doses without significant organ-specific toxicity; 3) effective modulation of molecular and genetic profile by cytotoxic agents that can be easily achieved in vitro but not in vivo; 4) treatment with cytotoxic agents can produce significant toxicity against normal organs, but not against tumor tissues. These results clearly indicates that though blood cytotoxic concentrations are achieved with the recommended cytotoxic doses; the delivery to tumor tissues represents a major therapeutic limitation regardless of the molecular profile of tumor cells.
It is now well established that tumors need continuous supply of nutrients and oxygen in order to grow. This is typically achieved by formation of new tumor vasculature. Therefore, antiangiogenic therapies have been considered in the treatment of tumors. Current antiangiogenic agent use, however, is fraught with various problems and new antiangiogenic techniques are needed. Another important determinant of tumor aggressiveness is tumor microvessel density. However, chemotherapeutic agents are often used without a consideration of the role tumor microvessel density (TMD) plays. Thus, there is a need in the field of cancer therapy for therapeutic approaches which take into consideration the modulation of tumor vasculature.